Journal Article

Identification of a new subset of lymph node stromal cells involved in regulating plasma cell homeostasis

Schaeuble, Karin, Hardie, Debbie L., Arenzana-Seisdedos, Fernando, Renevey, François, Peranzoni, Elisa, Scarpellino, Leonardo, Huang, Hsin-Ying, Luther, Sanjiv A., Cannelle, Hélène, Favre, Stéphanie, Vogt, Tobias K., Rivas-Caicedo, Ana, Donnadieu, Emmanuel, Pommier, Arnaud, Schneider, Pascal, Buckley, Christopher D.

2018

Overview

Antibody-secreting plasma cells (PCs) arise rapidly during adaptive immunity to control infections. The early PCs are retained within the reactive lymphoid organ where their localization and homeostasis rely on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by colocalizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRCs) that forms a dense meshwork throughout medullary cords of lymph nodes (LNs) where PCs reside. This medullary FRC type is shown to be anatomically, phenotypically, and functionally distinct from T zone FRCs, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRCs are the main cell type in contact with PCs guiding them in their migration. Medullary FRCs also represent a major local source of the PC survival factors IL-6, BAFF, and CXCL12, besides also producing APRIL. In vitro, medullary FRCs alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps in promoting the rapid development of humoral immunity, which is critical in limiting early pathogen spread.

• Publisher: National Academy of Sciences
• Subject: Adaptive control / Adaptive immunity / Animals / Antibody Formation / APRIL protein / B-Cell Activating Factor - immunology / Biological Sciences / BLyS protein / Cell survival / Chemokine CXCL12 - immunology / Cords / CXCL12 protein / Fibroblasts / Homeostasis / Homeostasis - immunology / Humoral immunity / Immunity / Immunoglobulins / Immunology and Inflammation / Infections / Interleukin 6 / Interleukin-6 - immunology / Leukocyte migration / Localization / Lymph nodes / Lymph Nodes - cytology / Lymph Nodes - immunology / Lymphatic system / Macrophages / Male / Medulla oblongata / Mice / Myeloid cells / Plasma / Plasma cells / Plasma Cells - cytology / Plasma Cells - immunology / PNAS Plus / Stromal cells / Stromal Cells - cytology / Stromal Cells - immunology / Survival